Relationship between sedimentation sign and morphological grade in symptomatic lumbar spinal stenosis.

PURPOSE: We aimed to study the relationship between two morphological parameters recently described on MRI images in relation to lumbar spinal stenosis (LSS): the first is the sedimentation sign (SedS) and the second is the morphological grading of lumbar stenosis. MATERIALS AND METHODS: MRIs from a total of 137 patients were studied. From those, 110 were issued from a prospective database of symptomatic LSS patients, of whom 73 were treated surgically and 37 conservatively based on symptom severity. A third group consisting of 27 subjects complaining of low back pain (LBP) served as control. Severity of stenosis was judged at disc level using the four A to D grade morphological classification. The presence of a SedS was judged at pedicle level, above or below the site of maximal stenosis. RESULTS: A positive SedS was observed in 58, 69 and 76 % of patients demonstrating B, C and D morphology, respectively, but in none with grade A morphology. The SedS was positive in 67 and 35 % of the surgically and conservatively treated patients, respectively, and in 8 % of the LBP group. C and D morphological grades were present in 97 and 35 % of patients in the surgically and conservatively treated group, respectively, and in 18 % of the LBP group. Presence of a positive SedS carried an increased risk of being submitted to surgery in the symptomatic LSS group (OR 3.5). This risk was even higher in the LSS patients demonstrating grade C or D morphology (OR 65). DISCUSSION AND CONCLUSION: One-third of surgically treated LSS patients do not present a SedS. This sign appears to be a lesser predictor of treatment modality in our setting of symptomatic LSS patients compared to the severity of stenosis judged by the morphological grade.

Spinal cord syndromes.

Spinal cord infarction is much rarer than cerebral stroke, but its early recognition is important as it may signify serious aortic conditions. The most frequent type is anterior spinal artery syndrome, presenting with bilateral weakness (usually paraparesis), impairment of spinothalamic sensation and preservation of deep sensation. Depending on its level, it may present with respiratory dysfunction. More rarely, posterior infarcts sparing spinothalamic sensation but involving lemniscal sensation may be encountered. Unilateral, central or transverse infarction may also be seen probably on account of different mechanisms. Other rarer forms of spinal ischemia also include spinal TIAs, venous infarction, fibrocartilaginous embolism and decompression sickness.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

PURPOSE: Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS. EXPERIMENTAL DESIGN: Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival. RESULTS: MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002). CONCLUSIONS: This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials. Clin Cancer Res; 21(20); 4733-9. ©2015 AACR.

Cell fusion reprogramming leads to a specific hepatic expression pattern during mouse bone marrow derived hepatocyte formation In Vivo

The fusion of bone marrow (BM) hematopoietic cells with hepatocytes to generate BM derived hepatocytes (BMDH) is a natural process, which is enhanced in damaged tissues. However, the reprogramming needed to generate BMDH and the identity of the resultant cells is essentially unknown. In a mouse model of chronic liver damage, here we identify a modification in the chromatin structure of the hematopoietic nucleus during BMDH formation, accompanied by the loss of the key hematopoietic transcription factor PU.1/Sfpi1 (SFFV proviral integration 1) and gain of the key hepatic transcriptional regulator HNF-1A homeobox A (HNF-1A/Hnf1a). Through genome-wide expression analysis of laser captured BMDH, a differential gene expression pattern was detected and the chromatin changes observed were confirmed at the level of chromatin regulator genes. Similarly, Tranforming Growth Factor-β1 (TGF-β1) and neurotransmitter (e.g. Prostaglandin E Receptor 4 [Ptger4]) pathway genes were over-expressed. In summary, in vivo BMDH generation is a process in which the hematopoietic cell nucleus changes its identity and acquires hepatic features. These BMDHs have their own cell identity characterized by an expression pattern different from hematopoietic cells or hepatocytes. The role of these BMDHs in the liver requires further investigation.

Spinal cord injury affects the interplay between visual and sensorimotor representations of the body.

The brain integrates multiple sensory inputs, including somatosensory and visual inputs, to produce a representation of the body. Spinal cord injury (SCI) interrupts the communication between brain and body and the effects of this deafferentation on body representation are poorly understood. We investigated whether the relative weight of somatosensory and visual frames of reference for body representation is altered in individuals with incomplete or complete SCI (affecting lower limbs' somatosensation), with respect to controls. To study the influence of afferent somatosensory information on body representation, participants verbally judged the laterality of rotated images of feet, hands, and whole-bodies (mental rotation task) in two different postures (participants' body parts were hidden from view). We found that (i) complete SCI disrupts the influence of postural changes on the representation of the deafferented body parts (feet, but not hands) and (ii) regardless of posture, whole-body representation progressively deteriorates proportionally to SCI completeness. These results demonstrate that the cortical representation of the body is dynamic, responsive, and adaptable to contingent conditions, in that the role of somatosensation is altered and partially compensated with a change in the relative weight of somatosensory versus visual bodily representations.

Short Report: Spinal Cord Stimulation in Thromboangiitis Obliterans and Secondary Raynaud's-Syndrome

Introduction: Spinal cord stimulation (SCS) may be a treatment option in limb ischemia occurring as a result of Thromboangiitis obliterans (TAO) or secondary Raynaud's-Syndrome (SRS). The impact of SCS on disease progression and micro-perfusion was prospectively evaluated during a follow-up (FU) of 4 years. Report: Under SCS, a significant increase in trans-cutaneous oxygen tension (tcpO2) was observed in TAO and a significant increase in systolic perfusion pressure at plethysmography was observed in SRS. Complete limb preservation was achieved in all patients who had reduced tobacco consumption. Discussion: SCS is an efficient therapeutic tool in TAO and SRS. Patient selection criteria are crucial for success.

Sacral fusion as an aid in age estimation

The degree of fusion at the anterior aspect of the sacral vertebrae has been scored in 242 male and female skeletons from the Lisbon documented collection, ranging in age from 16 to 59 years old. Statistical tests indicate a sex difference towards earlier fusion in young females compared with young males, as well as a clear association between degree of fusion and age. Similar results have been found in documented skeletal samples from Coimbra and Sassari, and the recommendations stated by these authors regarding age estimation have been positively tested in the Lisbon collection. Although more research from geographically diverse samples is required, a general picture of the pattern of sacral fusion and its associations with age and sex is emerging. We also provide a practical example of the usefulness of the sacrum in age estimation in a forensic setting, a mass grave from the Spanish Civil War. It is concluded that the scoring of the degree of fusion of the sacral vertebrae, specially of S1-2, can be a simple tool for assigning skeletons to broad age groups, and it should be implemented as another resource for age estimation in the study of human skeletal remains.

The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.

Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β-catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.

Spinal Cord T-Cell Infiltration in the Rat Spared Nerve Injury Model: A Time Course Study.

The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the spared nerve injury (SNI) model of neuropathic pain in Sprague Dawley adult male rats to assess proliferation, and/or protein/gene expression levels for microglia (Iba1), T-lymphocytes (CD2) and cytotoxic T-lymphocytes (CD8). In the dorsal horn ipsilateral to SNI, Iba1 and BrdU stainings revealed microglial reactivity and proliferation, respectively, with different durations. Iba1 expression peaked at D4 and D7 at the mRNA and protein level, respectively, and was long-lasting. Proliferation occurred almost exclusively in Iba1 positive cells and peaked at D2. Gene expression observation by RT-qPCR array suggested that T-lymphocytes attracting chemokines were upregulated after SNI in rat spinal cord but only a few CD2/CD8 positive cells were found. A pronounced infiltration of CD2/CD8 positive T-cells was seen in the spinal cord injury (SCI) model used as a positive control for lymphocyte infiltration. Under these experimental conditions, we show early and long-lasting microglia reactivity in the spinal cord after SNI, but no lymphocyte infiltration was found.

Reaction Kinetics and Viscosity Modelling in the Fusion Syntheses of Ca- and Ca/Mg-resinates

Rosin is a natural product from pine forests and it is used as a raw material in resinate syntheses. Resinates are polyvalent metal salts of rosin acids and especially Ca- and Ca/Mg- resinates find wide application in the printing ink industry. In this thesis, analytical methods were applied to increase general knowledge of resinate chemistry and the reaction kinetics was studied in order to model the non linear solution viscosity increase during resinate syntheses by the fusion method. Solution viscosity in toluene is an important quality factor for resinates to be used in printing inks. The concept of critical resinate concentration, c crit, was introduced to define an abrupt change in viscosity dependence on resinate concentration in the solution. The concept was then used to explain the non-inear solution viscosity increase during resinate syntheses. A semi empirical model with two estimated parameters was derived for the viscosity increase on the basis of apparent reaction kinetics. The model was used to control the viscosity and to predict the total reaction time of the resinate process. The kinetic data from the complex reaction media was obtained by acid value titration and by FTIR spectroscopic analyses using a conventional calibration method to measure the resinate concentration and the concentration of free rosin acids. A multivariate calibration method was successfully applied to make partial least square (PLS) models for monitoring acid value and solution viscosity in both mid-infrared (MIR) and near infrared (NIR) regions during the syntheses. The calibration models can be used for on line resinate process monitoring. In kinetic studies, two main reaction steps were observed during the syntheses. First a fast irreversible resination reaction occurs at 235 °C and then a slow thermal decarboxylation of rosin acids starts to take place at 265 °C. Rosin oil is formed during the decarboxylation reaction step causing significant mass loss as the rosin oil evaporates from the system while the viscosity increases to the target level. The mass balance of the syntheses was determined based on the resinate concentration increase during the decarboxylation reaction step. A mechanistic study of the decarboxylation reaction was based on the observation that resinate molecules are partly solvated by rosin acids during the syntheses. Different decarboxylation mechanisms were proposed for the free and solvating rosin acids. The deduced kinetic model supported the analytical data of the syntheses in a wide resinate concentration region, over a wide range of viscosity values and at different reaction temperatures. In addition, the application of the kinetic model to the modified resinate syntheses gave a good fit. A novel synthesis method with the addition of decarboxylated rosin (i.e. rosin oil) to the reaction mixture was introduced. The conversion of rosin acid to resinate was increased to the level necessary to obtain the target viscosity for the product at 235 °C. Due to a lower reaction temperature than in traditional fusion synthesis at 265 °C, thermal decarboxylation is avoided. As a consequence, the mass yield of the resinate syntheses can be increased from ca. 70% to almost 100% by recycling the added rosin oil.

Sensor Fusion of Proprioception, Force and Vision in Estimation and Robot

Sensor-based robot control allows manipulation in dynamic environments with uncertainties. Vision is a versatile low-cost sensory modality, but low sample rate, high sensor delay and uncertain measurements limit its usability, especially in strongly dynamic environments. Force is a complementary sensory modality allowing accurate measurements of local object shape when a tooltip is in contact with the object. In multimodal sensor fusion, several sensors measuring different modalities are combined to give a more accurate estimate of the environment. As force and vision are fundamentally different sensory modalities not sharing a common representation, combining the information from these sensors is not straightforward. In this thesis, methods for fusing proprioception, force and vision together are proposed. Making assumptions of object shape and modeling the uncertainties of the sensors, the measurements can be fused together in an extended Kalman filter. The fusion of force and visual measurements makes it possible to estimate the pose of a moving target with an end-effector mounted moving camera at high rate and accuracy. The proposed approach takes the latency of the vision system into account explicitly, to provide high sample rate estimates. The estimates also allow a smooth transition from vision-based motion control to force control. The velocity of the end-effector can be controlled by estimating the distance to the target by vision and determining the velocity profile giving rapid approach and minimal force overshoot. Experiments with a 5-degree-of-freedom parallel hydraulic manipulator and a 6-degree-of-freedom serial manipulator show that integration of several sensor modalities can increase the accuracy of the measurements significantly.

Bioactive Glass in Lumbar Spondylodesis. A Pre-Clinical and Clinical Study

Bioactive glasses (BGs) form a group of synthetic, surface-active, composition-dependent, silica-based biomaterials with osteoconductive, osteopromotive, and even angiogenic, as well as antibacterial, properties. A national interdisciplinary research group, within the Combio Technology Program (2003–2007), developed a porous load-bearing composite for surgical applications made of BG 1–98 and polymer fibers. The pre-clinical part of this thesis focused on the in vitro and in vivo testing of the composite materials in a rabbit femur and spinal posterolateral fusion model. The femur model failed to demonstrate the previously seen positive effect of BG 1–98 on osteogenesis, probably due to the changed resorption properties of BG in the form of fibers. The spine study was terminated early due to adverse events. In vitro cultures showed the growth inhibition of human mesenchymal stems next to BG 1–98 fibers and radical pH changes. A prospective, long-term, follow-up study was conducted on BG–S53P4 and autogenous bone used as bone graft substitutes for instrumented posterolateral spondylodesis in the treatment of degenerative spondylolisthesis (n=17) and unstable burst fractures (n=10) during 1996–1998. The operative outcome was evaluated from X-rays and CT scans, and a clinical examination was also performed. On the BG side, a solid fusion was observed in the CT scans of 12 patients, and a partial fusion was found in 5 patients, the result being a total fusion rate in all fusion sites (n=41) 88% for levels L4/5 and L5/S1 in the spondylolisthesis group. In the spine fracture group, solid fusion was observed in five patients, and partial fusion was found in five resulting in a total fusion rate of 71% of all fusion sites (n=21). The pre-clinical results suggest that under certain conditions the physical form of BG can be more critical than its chemical composition when a clinical application is designed. The first long-term clinical results concerning the use of BG S53P4 as bone graft material in instrumented posterolateral spondylodesis seems to be a safe procedure, associated with a very low complication rate. BG S53P4 used as a stand-alone bone substitute cannot be regarded as being as efficient as AB in promoting solid fusion.